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[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

: Viral gene transfer or transgenic animals are commonly used technologies to alter gene expression in the adult brain, although these approaches lack spatial specificity and are time consuming.

We delivered plasmid DNA locally into the brain of adult C57BL/6 mice in vivo by voltage- and current-controlled electroporation.

In conclusion, low current-controlled electroporation is an excellent approach for electroporation in the adult brain, i.e., gene function can be influenced locally at a high level with no mortality and minimal tissue damage.

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[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Issues and Ethical Problems of Stem Cell Therapy - Where is Hippocrates?

Stem cells and their therapeutic use present many questions associated with ethical problems in medicine.

There is great effort on the part of physicians to help millions of patients while there are ethical problems with the use of new methods and technologies and all of these are affected by economic and political influences.

How will the current generation deal with these problems?

Medicine, in this begard, is experiencing a stormy evolution of human culture in the relationships between disease, patient and doctor.

Philosophy approaches the same juncture of human culture, but seemingly from the other side.

Both disciplines are facing a great problem: How to unite the content of current human morality and the desire for health?

Both philosophers and physicians perceive this deficit in human culture as it does not provide immediately usable normatives, which the living generation of healthy and ill is waiting for.

It may be said that medicine, as many times before, has reached a stage where it cannot rely only on the proved axiologic values from the past, ethical normatives or cultivated moral sense of its subjects.

Medicine has no other alternative than to take an active part in resolution of interdisciplinary problems originating from philosophic-biologic or philosophic-medical inquiries of axiologic, ethical, and moral issues.

Our paper indicates some ways of the search in forming ethical principles of the stem-cell therapy from the view of biologists and physicians.

New ways are recommended in theoretical-methodological interdisciplinary research, especially, in theoretical and experimental biology, and theoretical and clinical medicine, as well as philosophy.

In this paper important ethical problems are pointed out in order to find answers to some key problems connected with cell therapy and the use of stem cells.

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[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

In this study we show that lentiviral delivery of the gene encoding ER-α to the hippocampus of adult ER-α-knockout (ER-αKO) mice restores hippocampal responsiveness to estrogen and rescues spatial learning.

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[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

The aim of this study was to analyze the possible association of TP53 mutation, p53 overexpression, and p53 codon 72 polymorphism with susceptibility to apoptosis in adult Brazilian patients with diffuse astrocytomas.

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[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Association of adolescent and young adult cancer treatment trial activity with a national mortality reduction benefit in the United States.

: 6605 Background: Adolescent and young adult (AYA) cancer patients in the U.S. have had less mortality and survival improvement than have children or older adults with cancer.

Among 15-29 year-olds nearly all of the increased accrual occurred in patients with leukemia or lymphoma, in whom the ratio of the national death rate to SEER incidence fell below the projected linear regression for this ratio in each year during 2002-2005.

CONCLUSIONS: In the U.S., COG is now contributing more AYA patients to NCTT than any adult cooperative group, suggesting that the adult-treating groups and cancer centers have increased capability to increase AYA accrual and should complement the pediatric effort.

These favorable trends should encourage implementation of the clinical trial recommendations of the NCI Program Review Group in AYA Oncology ( http://planning.cancer.gov/disease/AYAO_PRG_Report_2006_FINAL.pdf ) that are being implemented in part by the LIVESTRONG Young Adult Alliance (Closing the Gap: A Strategic Plan).

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(PMID = 27961733.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

METHODS: Adult patients with CLL diagnosed by the NCI-WG criteria who had received at least one previous fludarabine-based therapy and subsequently progressed or relapsed with ECOG performance status (PS) ≤3 and normal organ functions were included.

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(PMID = 27961474.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Six intact young adult cynomolgus monkeys received a single 10 µl injection of AAV2/1-GFP, AAV2/5-GFP, or AAV2/8-GFP pseudotyped vectors into the caudate nucleus and putamen bilaterally in a pattern that resulted in each capsid serotype being injected into at least four striatal sites.

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[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

METHODS: A prospective, observational unicenter study of adult patients receiving their first chemotherapy cycle was performed.

Medical oncologists and oncology nurses also estimated the incidence of acute (Day 1) and delayed (Days 2-5) CINV after first administration of HEC and MEC.

Observed incidence rates of acute and delayed CINV were compared with physician/nurse predictions.

Acute nausea and emesis were observed in 14.3% and 2.4% respectively of HEC patients receiving Aprepitant, and delayed nausea and emesis were observed in 14.3% and 7.1% of these patients, respectively.

[Publication-country] United States

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

: e20660 Background: The authors determined the incidence of acute and delayed chemotherapy-induced nausea and vomiting (CINV) among new patients (pts) receiving chemotherapy with modern antiemetic prophylaxis in 2008.

METHODS: A prospective observational study of adult cancer pts receiving, for the first time, moderately or highly emetogenic chemotherapy (MEC or HEC) was performed.

Study participants were called on day 2 and day 8, after first and second cycle, to evaluate acute and delayed emesis according a 10-item questionnaire.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

: 8547 Background: Increased late mortality and morbidity have been observed among adult survivors of Hodgkin lymphoma (HL) treated in childhood, but are less well characterized for patients treated in adulthood.

METHODS: We investigated the late mortality and morbidity of adult patients treated at our center from 1975 to 2000.

These findings underscore the importance of efforts directed at prevention of and early intervention for late morbidity in adult survivors of HL.

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(PMID = 27960964.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[Publication-country] United States

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Furthermore, we retrospectively analyzed whether outcome of osteosarcoma in young adult patients is different when treatment took place in a pediatric or an adult oncology department.

Overall survival of patients aged 14-20 years was not significant different when treated in a pediatric oncology department as compared to treatment in an adult department (57.9% vs. 47.4%, p= 0.705) .

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(PMID = 27963889.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

The most frequent somatic copy number alteration was deletion on 7p12 of IKZF1 (68/106, 64%), which encodes the transcription factor Ikaros required for the earliest stages of lymphoid lineage commitment.

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(PMID = 27964054.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] A phase II study of the tolerability and activity of weekly vincristine sulfate liposomes injection (VSLI) in adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in second relapse or progressing following two antileukemia treatment lines.

METHODS: Eligible adult subjects received single agent intravenous VSLI at a dose of 2.25 mg/m<sup>2</sup> weekly with no dose cap.

This population typically has a very low response rate to anti-leukemia therapies.

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(PMID = 27961424.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

: 7049 Since the activation-induced cytidine deaminase (AID) enzyme can target non-immunoglobulin (Ig) genes and may even act as a genome-wide mutator, we investigated AID expression in BCR-ABL1-positive ALL and in chronic myeloid leukemia (CML) at the time of progression to blast crisis.

On the 61 de novo adult BCR-ABL1-positive ALL patients (pts), AID mRNA and protein were detected in 36 (59%); their expression correlated with BCR-ABL1 transcript levels and disappeared after treatment with tyrosine kinase inhibitors at the time of remission.

AID expression was also found in lymphoid blast crisis CML (50%), but not in myeloid lineage or in chronic phase CML.

Our findings show that BCR-ABL1-positive ALL cells aberrantly express different isoforms of AID that can act as mutator outside the Ig gene loci in promoting genetic instability in leukemia cells.

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(PMID = 27961429.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

METHODS: We convened an international panel (N = 17) of experts in pediatric and adult hematological malignancies and solid tumors (ST) to develop a medical decision tree for the P and T of TLS based on the risk classification (low, medium, high) and management recommendations of Coiffier et al (J Clin Oncol.

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(PMID = 27963935.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[Publication-type] Journal Article

[Publication-country] United States

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Transplantation in adult ALL.

The value of the allogeneic graft-versus-leukemia effect in adultacute lymphoblastic leukemia (ALL) has now been conclusively demonstrated and confirmed.

Clinical indications to harness the allogeneic effect will mature as the true value of pediatric protocols in adult patients and the safety and efficacy of a sibling, unrelated and reduced intensity transplant emerge in this disease.

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(PMID = 20008244.001).

[ISSN] 1520-4383

[Journal-full-title] Hematology. American Society of Hematology. Education Program

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

The role of autologous hematopoietic SCT (autoHSCT) in the treatment of high-risk (HR) adult ALL is controversial.

In this study, we retrospectively analyzed the results of autoHSCT according to the status of minimal residual disease (MRD) at transplantation, as a joint analysis of the European Study Group for Adult ALL (EWALL).

In a cohort of Ph-negative ALL, the probability of leukemia-free survival at 5 years was higher for patients with MRD <0.1% compared with those with MRD > or = 0.1% (57 vs 17%, P=0.0002).

We conclude that MRD determines the outcome of autoHSCT in HR adult ALL.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

The impact of silencing tumor suppressor genes involved in cell proliferation in adult and pediatric ALL is still unknown.

Comparisons with adult ALL showed that p57 clearly differed in children (7% methylation) and adults (50% methylation).

While >20% of adult ALL Ph1 chromosome-negative undergo methylation of p73, p57, and p15, only 3% of childhood ALL carried such anomalies, which is very significant when a higher fraction of pediatric patients has non-Ph1 ALL than do the adult patients.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

METHODS: Adult pts with a diagnosis of DTC treated with single agent sorafenib (SOR) or sunitinib (SUN), and who had a baseline and at least 1 follow-up (f/u) scan after 3 months (mos) of therapy, were included.

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(PMID = 27961926.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Assessment of efficacy, safety, and tolerability of aprepitant in adult patients with chemotherapy-induced vomiting.

The present study was undertaken to assess efficacy, safety, and tolerability of Aprepitant in adult patients with chemotherapy induced nausea and vomiting.

METHODS: The study was conducted as a prospective, multicenter, randomized, open label, single group, phase III study in adult patients with chemotherapy induced nausea and vomiting and patients admitted to hospital for any type of cancer.

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(PMID = 27962017.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

METHODS: Adult Pts with T315I+ CML following TKI failure received OM induction at 1.25 mg/m<sup>2</sup> subcutaneous (SC) twice daily (BID) for 14 days every 28 days followed by maintenance at 1.25 mg/m<sup>2</sup> SC BID for 7 days every 28 days (maintenance after at least one induction cycle and achievement of hematologic response).

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(PMID = 27961380.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

In this work, the x-ray spectra predicted by various computational models used in the diagnostic radiology and mammography energy range have been assessed by comparison with measured spectra and their effect on the calculation of absorbed dose and effective dose (ED) imparted to the adult ORNL hermaphroditic phantom quantified.

The MCNP4C-based Monte Carlo calculations showed there is no discernable discrepancy in the calculation of absorbed dose and ED in the adult ORNL hermaphroditic phantom when using different computational models for generating the x-ray spectra.

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[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] CD10- pre-B acute lymphoblastic leukemia (ALL) is a distinct high-risk subgroup of adult ALL associated with a high frequency of MLL aberrations: results of the German Multicenter Trials for Adult ALL (GMALL).

Our data identify CD10- cytoplasmic immunoglobulin-positive pre-B ALL as a rare (2.2%) but distinct immuno-subtype of adult ALL that is characterized by a high MLL rearrangement rate and a worse outcome.

CONCLUSIONS: Using data-trimming of whole genome expression studies, we defined and validated a nine-gene signature that is an independent predictive marker for therapy response in adult Ph+ ALL patients.

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(PMID = 27961387.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

: s1 Forty-five years ago adult AL was incurable.

Publication of the French-American-British classification 34 years ago resulted in acceptance that morphology and cytochemistry separated AL into two different diseases, acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), that required separate treatment.

The most striking example of increased curability of AL is acute promyelocytic leukemia, in which targeted therapy combined with chemotherapy has increased survival from a 2-week median to an 80% cure rate.

Among adult de novo AML 40%-45% are cytogenetically normal (CN); the striking molecular heterogeneity of CN-AML is now being recognized and promises to allow individualized approaches that improve substantially upon the current cure rate of 40%.

In adult ALL the major adverse subgroup has a Philadelphia chromosome (PH+).

New approaches to studying the leukemia genome and epigenome should improve our understanding of AL heterogeneity, identify new therapeutic targets, and allow the cure of most patients.

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(PMID = 27962366.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

: 5015 Background: From July 1995 to December 2003, 602 adult patients from Sweden and Norway with metastatic testicular NSGCT were included in a population-based multicenter SWENOTECA protocol with strict guidelines for staging, treatment and follow-up.

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(PMID = 27962902.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

METHODS: A retrospective chart review was performed that included all adult patients with existing VP shunts requiring PEG placement at a single university medical center over an approximate 9-year period from July 1995 to March 2004.

As the total number of adult patients requiring a PEG after VP shunt placement is low, multicenter studies should be carried out to better stratify this risk.

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Four genes (p15, p16, RARbeta, FHIT) had methylation in both diseases, four genes (p14, Rb, MLH1, DAPK) showed no methylation in both diseases, and the two genes (APC, RIZ) demonstrated methylation only in adult ALL.

Methylation of the RARbeta was more frequent in adult ALL than that in childhood ALL (p=0.01).

The number of patients with methylation of multiple genes was higher in adult ALL than that in childhood ALL (p=0.006).

Moreover, overall frequency of methylation was higher in adult ALL than that in childhood ALL (p=0.01).

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

BACKGROUND: Despite recent improvements in the treatment of acute lymphoblastic leukemia (ALL), adult patients still have an overall poor outcome.

The authors sought to assess if protein kinases (PKs), frequently deregulated in cancer, show an altered expression pattern and can be considered as suitable therapeutic targets in adult ALL.

METHODS: The authors studied the PK gene expression profile by oligonucleotide arrays in 133 adult ALL samples at the onset of the disease and subsequently performed in vitro experiments to evaluate the sensitivity to first- and second-generation PK inhibitors of a set of ALL cell lines, as well as of primary ALL cells.

RESULTS: The study documents a distinctive PK signature for different adult ALL subgroups; the PKs identified include several tyrosine kinase (TK) genes, especially in E2A/PBX+ B-lineage ALL (B-ALL), B-ALL without known molecular abnormalities, and T-lineage ALL.

CONCLUSIONS: These results indicate that second-generation TK inhibitors may be effective in ALL subsets other than BCR/ABL+B-ALL and provide the rationale for testing the impact of the newly developed TK inhibitors in the management of adult ALL patients.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title]Adultacute lymphoblastic leukemia: concepts and strategies.

Acute lymphoblastic leukemia (ALL), a clonal expansion of hematopoietic blasts, is a highly heterogeneous disease comprising many entities for which distinct treatment strategies are pursued.

An expansion of new drugs, more reliable immunologic and molecular techniques for the assessment of minimal residual disease, and efforts at more precise risk stratification are generating new aspects of adult ALL therapy.

For this review, the authors summarized pertinent and recent literature on ALL biology and therapy, and they discuss current strategies and potential implications of novel approaches to the management of adult ALL.

PATIENTS AND METHODS: DNA microarrays were used to profile a set of 54 adult ALL specimens from the Medical Research Council UKALL XII/Eastern Cooperative Oncology Group E2993 trial (21 p185BCR-ABL-positive, 16 p210BCR-ABL-positive and 17 BCR-ABL-negative specimens).

RESULTS: Using supervised and unsupervised analysis tools, we detected significant transcriptomic changes in BCR-ABL-positive versus -negative specimens, and assessed their validity in an independent cohort of 128 adult ALL specimens.

[Chemical-registry-number] EC 2.7.10.2 / Fusion Proteins, bcr-abl

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Clinical characteristics, biologic features and outcome for young adult patients with acute lymphoblastic leukaemia.

Young adult patients with acute lymphoblastic leukaemia (ALL) represent a unique epidemiologic subgroup in that therapy may be provided by either adult or paediatric oncologists.

There seem to be no differences in presenting clinical features, immunophenotypic characteristics, or cytogenetic abnormalities for young adult ALL patients treated on paediatric or adult protocols with the exception of median age (16-paediatric trials versus 19-adult trials).

Compared with patients 1-9 years, young adult ALL patients have a lower incidence of favourable cytogenetics t(12;.

Compared with patients >30 years, young adult ALL patients have a significantly lower incidence of the t(9; 22).

In multiple studies, there is a consistent, large event-free survival and survival advantage for young adult patients treated on paediatric versus adult protocols.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Long-term outcomes of adults with acute lymphoblastic leukemia after autologous or unrelated donor bone marrow transplantation: a comparative analysis by the National Marrow Donor Program and Center for International Blood and Marrow Transplant Research.

We analysed data from two transplant registries to determine outcomes between Auto and URD HSCT for 260 adult ALL patients in first (CR1) or second (CR2) CR.

[Other-IDs] NLM/ NIHMS112862; NLM/ PMC2844086

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Treating the "older" adult with acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) in adults is a rare disease.

This article describes the results of chemotherapy and blood and marrow transplantation for Philadelphia chromosome negative and positive adult ALL in the "older" adult patient, but also critically examines the major controversies and suggests how they might be resolved.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

The (1;19)(q23;p13) translocation, leading to the production of the E2A/PBX1 fusion transcript, is one of the most common translocations in pediatric B-lineage acute lymphoblastic leukemia (ALL).

Only few data are available concerning t(1;19)(q23;p13) in adult ALL.

We describe three cases of adult ALL carrying the t(1;19)(q23;p13), who were all characterized by an aggressive clinical course and short survival, and discuss the molecular features of the disease as recently identified by gene expression profiling.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

We have studied forty Chinese adult ALL patients at newly diagnosis, using standard primers and protocols of BIOMED-2 multiplex PCR, to determine the feasibility of Ig and TCR gene rearrangements as diagnostic and patient-specific MRD-RQ-PCR targets for molecular monitoring.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

It plays an important role in the leukemia pathogenesis.

This phenomenon is frequently observed in acute lymphoblastic leukemia (ALL) and results in the functional inactivation of its associated genes.

The aim of this study is to investigate the frequency and the prognostic impact of p15 and p73 genes methylation in adultacute lymphoblastic leukemia patients.

PATIENTS AND METHODS: Methylation-specific polymerase chain reaction (PCR) was used to analyze methylation of the p15 and p73 genes in 51 newly diagnosed adult ALL patients.

The leukemia free survival was not affected by the methylation status of single gene p15 or p73, but tended to be worse in patients with methylated p15, p73 or both genes when compared to patients without methylation (p=0.08).

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] AAV2/8-mediated Correction of OTC Deficiency Is Robust in Adult but Not Neonatal Spf<sup>ash</sup> Mice.

In this study, we investigated metabolic correction in neonatal and adult male OTC-deficient Spf<sup>ash</sup> mice following adeno-associated virus (AAV)2/8-mediated delivery of the murine OTC complementary DNA under the transcriptional control of a liver-specific promoter.

Substantially supraphysiological levels of OTC enzymatic activity were readily achieved in both adult and neonatal mice following a single intraperitoneal (i.p.) injection, with metabolic correction in adults being robust and life-long.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

A high incidence of disseminated intravascular coagulation (DIC) in adult patients with acute lymphoblastic leukemia (ALL) is reported.

However, studies comprising both childhood and adult patients are sparse and the clinical relevance of DIC in ALL patients has been a conflicting issue.

Coagulation profiles at presentation and within seven days after starting remission-induction therapy of 44 childhood and 51 adult ALL patients were studied.

At presentation, two childhood (5%) and 11 adult (22%) patients had DIC (p<0.05).

After starting therapy, four of 27 childhood (15%) and 14 of 33 adult (42%) patients screened for coagulopathy developed DIC (p<0.05).

In the adult cases, DIC was more frequently complicated with FAB subtype L2 than L1 (p<0.05).

In the adult patients, two patients with DIC had WHO grade 3 hemorrhage and the other hemorrhagic complications were minor hemorrhages.

While milder induction therapies starting with corticosteroid given for childhood cases should be taken into consideration when comparing the incidences of DIC after therapy, the findings indicated that childhood and adult ALL may differ in the procoagulant characteristics.

Morphological distinction between L1 and L2 appears to have relevance in the procoagulant activity in adult ALL.